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2 - Genetics of human and rodent body weight regulation

Published online by Cambridge University Press:  15 September 2009

Karine Clément
Affiliation:
Hôtel-Dieu Service de Nutrition Place du Parvis, Notre-Dame 75004, Paris, France
Jenni Harvey
Affiliation:
University of Dundee
Dominic J. Withers
Affiliation:
Imperial College of Science, Technology and Medicine, London
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Publisher: Cambridge University Press
Print publication year: 2008

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References

Ardlie, K. G., Lunetta, K. L. & Seielstad, M. (2002). Testing for population subdivision and association in four case-control studies. Am. J. Hum. Genet. 71, 304–11.CrossRefGoogle ScholarPubMed
Argyropoulos, G., Rankinen, T., Neufeld, D. R.et al. (2002). A polymorphism in the human agouti-related protein is associated with late-onset obesity. J. Clin. Endocrinol. Metab. 87, 4198–202.CrossRefGoogle ScholarPubMed
Bahary, N., Leibel, R. L., Joseph, L. & Friedman, J. M. (1990). Molecular mapping of the mouse db mutation. Proc. Natl. Acad. Sci. USA 87, 8642–6.CrossRefGoogle ScholarPubMed
Bai, F., Rankinen, T., Charbonneau, C.et al. (2004). Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium. J. Med. Genet. 41, 350–3.CrossRefGoogle ScholarPubMed
Baker, M., Gaukrodger, N., Mayosi, B. M.et al. (2005). Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study. Diabetes 54, 2492–6.CrossRefGoogle ScholarPubMed
Balthasar, N., Dalgaard, L. T., Lee, C. E.et al. (2005). Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493–505.Google ScholarPubMed
Biebermann, H., Krude, H., Elsner, A.et al. (2003). Autosomal-dominant mode of inheritance of a melanocortin-4 receptor mutation in a patient with severe early-onset obesity is due to a dominant-negative effect caused by receptor dimerization. Diabetes 52, 2984–8.CrossRefGoogle Scholar
Biebermann, H., Castaneda, T. R., Landeghem, F.et al. (2006). A role for beta-melanocyte-stimulating hormone in human body-weight regulation. Cell Metab. 3, 141–6.CrossRefGoogle ScholarPubMed
Boucher, N., Lanouette, C. M., Larose, M.et al. (2002). A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence. Mol. Med. 8, 158–65.Google ScholarPubMed
Boutin, P., Dina, C., Vasseur, F.et al. (2003). GAD2 on Chromosome 10p12 is a candidate gene for human obesity. PLoS Biol 1, E68.CrossRefGoogle ScholarPubMed
Branson, R., Potoczna, N., Kral, J. G.et al. (2003). Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N. Engl. J. Med. 348, 1096–103.CrossRefGoogle ScholarPubMed
Bultman, S. J., Michaud, E. J. & Woychik, R. P. (1992). Molecular characterization of the mouse agouti locus. Cell 71, 1195–204.CrossRefGoogle ScholarPubMed
Butler, A. A. (2006). The melanocortin system and energy balance. Peptides 27, 281–90.CrossRefGoogle ScholarPubMed
Carroll, K., Gomez, C. & Shapiro, L. (2004). Tubby proteins: the plot thickens. Nat. Rev. Mol. Cell Biol. 5, 55–63.CrossRefGoogle ScholarPubMed
Carroll, L., Voisey, J. & Daal, A. (2005). Gene polymorphisms and their effects in the melanocortin system. Peptides 26, 1871–85.CrossRefGoogle ScholarPubMed
Challis, B. G., Pritchard, L. E., Creemers, J. W.et al. (2002). A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum. Mol. Genet. 11, 1997–2004.CrossRefGoogle ScholarPubMed
Chen, A. S., Marsh, D. J., Trumbauer, M. E.et al. (2000). Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26, 97–102.Google ScholarPubMed
Chung, W. K. & Leibel, R. L. (2005). Molecular physiology of syndromic obesities in humans. Trends Endocrinol. Metab. 16, 267–72.CrossRefGoogle ScholarPubMed
Clement, K., Vaisse, C., Lahlou, N.et al. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392, 398–401.CrossRefGoogle ScholarPubMed
Coleman, D. L. (1973). Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 9, 294–8.CrossRefGoogle ScholarPubMed
Coll, A. P., Farooqi, I. S., Challis, B. G., Yeo, G. S. & O'Rahilly, S. (2004). Proopiomelanocortin and energy balance: insights from human and murine genetics. J. Clin. Endocrinol. Metab. 89, 2557–62.CrossRefGoogle ScholarPubMed
Luca, C., Kowalski, T. J., Zhang, Y.et al. (2005). Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J. Clin. Invest. 115, 3484–93.CrossRefGoogle ScholarPubMed
Rijke, C. E., Jackson, P. J., Garner, K. M.et al. (2005). Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. Biochem. Pharmacol. 70, 308–16.CrossRefGoogle ScholarPubMed
Dempfle, A., Hinney, A., Heinzel-Gutenbrunner, M.et al. (2004). Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index. J. Med. Genet. 41, 795–800.CrossRefGoogle ScholarPubMed
Dong, C., Li, W. D., Li, D. & Price, R. A. (2004). Interaction between obesity-susceptibility loci in chromosome regions 2p25-p24 and 13q13-q21. Eur. J. Hum. Genet. 13, 102–8.CrossRefGoogle Scholar
Dubern, B., Clement, K., Pelloux, V.et al. (2001). Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J. Pediatr. 139, 204–9.CrossRefGoogle ScholarPubMed
Durand, E., Boutin, P., Meyre, D.et al. (2004). Polymorphisms in the amino acid transporter solute carrier family 6 (neurotransmitter transporter) member 14 gene contribute to polygenic obesity in French Caucasians. Diabetes 53, 2483–6.CrossRefGoogle ScholarPubMed
Elefteriou, F., Ahn, J. D., Takeda, S.et al. (2005). Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434, 514–20.CrossRefGoogle Scholar
Farooqi, I. S. & O'Rahilly, S. (2004). Monogenic human obesity syndromes. Recent Prog. Horm. Res. 59, 409–24.CrossRefGoogle ScholarPubMed
Farooqi, I. S. & O'Rahilly, S. (2005). Monogenic obesity in humans. Annu. Rev. Med. 56, 443–58.CrossRefGoogle ScholarPubMed
Farooqi, I. S., Yeo, G. S., Keogh, J. M.et al. (2000). Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J. Clin. Invest. 106, 271–9.CrossRefGoogle ScholarPubMed
Farooqi, I. S., Keogh, J. M., Kamath, S.et al. (2001). Partial leptin deficiency and human adiposity. Nature 414, 34–5.CrossRefGoogle ScholarPubMed
Farooqi, I. S., Matarese, G., Lord, G. M.et al. (2002). Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110, 1093–103.CrossRefGoogle ScholarPubMed
Farooqi, I. S., Keogh, J. M., Yeo, G. S.et al. (2003a). Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 348, 1085–95.CrossRefGoogle Scholar
Farooqi, I. S., Yeo, G. S. & O'Rahilly, S. (2003b). Binge eating as a phenotype of melanocortin 4 receptor gene mutations. N. Engl. J. Med. 349, 606–9.Google Scholar
Farooqi, I. S., Drop, S., Clements, A.et al. (2006). Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes. 55, 2549–53.CrossRefGoogle ScholarPubMed
Feng, N., Young, S. F., Aguilera, G.et al. (2005). Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity. Diabetes 54, 2663–7.CrossRefGoogle ScholarPubMed
Friedman, J. M., Leibel, R. L., Siegel, D. S., Walsh, J. & Bahary, N. (1991). Molecular mapping of the mouse ob mutation. Genomics 11, 1054–62.CrossRefGoogle ScholarPubMed
Gotoda, T. (2003). Binge eating as a phenotype of melanocortin 4 receptor gene mutations. N. Engl. J. Med. 349, 606–609; author reply 606–609.Google ScholarPubMed
Govaerts, C., Srinivasan, S., Shapiro, A.et al. (2005). Obesity-associated mutations in the melanocortin 4 receptor provide novel insights into its function. Peptides 26, 1909–19.CrossRefGoogle ScholarPubMed
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A. & Friedman, J. M. (1997). Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc. Natl. Acad. Sci. USA 94, 8878–83.CrossRefGoogle ScholarPubMed
Hebebrand, J., Friedel, S., Schauble, N., Geller, F. & Hinney, A. (2003). Perspectives: molecular genetic research in human obesity. Obes. Rev. 4, 139–46.CrossRefGoogle ScholarPubMed
Hebebrand, J., Geller, F., Dempfle, A.et al. (2004). Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations. Mol. Psychiatry 9, 796–800.CrossRefGoogle Scholar
Heid, I. M., Vollmert, C., Hinney, A.et al. (2005). Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys. J. Med. Genet. 42, e21.CrossRefGoogle ScholarPubMed
Herpertz, S., Siffert, W. & Hebebrand, J. (2003). Binge eating as a phenotype of melanocortin 4 receptor gene mutations. N. Engl. J. Med. 349, 606–9.Google ScholarPubMed
Hinney, A., Schmidt, A., Nottebom, K.et al. (1999). Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J. Clin. Endocrinol. Metab. 84, 1483–6.CrossRefGoogle Scholar
Hixson, J. E., Almasy, L., Cole, S.et al. (1999). Normal variation in leptin levels is associated with polymorphisms in the proopiomelanocortin gene, POMC. J. Clin. Endocrinol. Metab. 84, 3187–91.Google ScholarPubMed
Holder, J. L. Jr., Butte, N. F. & Zinn, A. R. (2000). Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum. Mol. Genet. 9, 101–8.Google ScholarPubMed
Huszar, D., Lynch, C. A., Fairchild-Huntress, V.et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–41.CrossRefGoogle ScholarPubMed
Irani, B. G., Xiang, Z., Moore, M. C., Mandel, R. J. & Haskell-Luevano, C. (2005). Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse. Biochem. Biophys. Res. Commun. 326, 638–44.CrossRefGoogle ScholarPubMed
Jackson, R. S., Creemers, J. W., Ohagi, S.et al. (1997). Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat. Genet. 16, 303–6.CrossRefGoogle ScholarPubMed
Jackson, R. S., Creemers, J. W., Farooqi, I. S.et al. (2003). Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J. Clin. Invest. 112, 1550–60.CrossRefGoogle ScholarPubMed
Jacobson, P., Ukkola, O., Rankinen, T.et al. (2002). Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort. J. Clin. Endocrinol. Metab. 87, 4442–6.CrossRefGoogle Scholar
Kennedy, G. C. (1953). The role of depot fat in the hypothalamic control of food intake in the rat. Proc. R. Soc. Lond. B. Biol. Sci. 140, 578–96.CrossRefGoogle ScholarPubMed
Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G. & Gruters, A. (1998). Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 19, 155–7.CrossRefGoogle ScholarPubMed
Krude, H., Biebermann, H., Schnabel, D.et al. (2003). Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH 4-10. J. Clin. Endocrinol. Metab. 88, 4633–40.CrossRefGoogle Scholar
Lahlou, N., Clement, K., Carel, J. C.et al. (2000). Soluble leptin receptor in serum of subjects with complete resistance to leptin: relation to fat mass. Diabetes 49, 1347–52.CrossRefGoogle ScholarPubMed
Lander, E. S. (1996). The new genomics: global views of biology. Science 274, 536–9.CrossRefGoogle ScholarPubMed
Larsen, L. H., Echwald, S. M., Sorensen, T. I., Andersen, T., Wulff, B. S. & Pedersen, O. (2004). Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. J. Clin. Endocrinol. Metab. 90, 219–24.CrossRefGoogle ScholarPubMed
Lee, Y. S., Challis, B. G., Thompson, D. A.et al. (2006). A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab. 3, 135–40.CrossRefGoogle ScholarPubMed
Li, W. D., Joo, E. J., Furlong, E. B.et al. (2000). Melanocortin 3 receptor (MC3R) gene variants in extremely obese women. Int. J. Obes. Relat. Metab. Disord. 24, 206–10.CrossRefGoogle ScholarPubMed
Licinio, J., Caglayan, S., Ozata, M.et al. (2004). Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc. Natl. Acad. Sci. USA 101, 4531–6.CrossRefGoogle ScholarPubMed
Loos, R. J., Rankinen, T., Rice, T.et al. (2005). Two ethnic-specific polymorphisms in the human Agouti-related protein gene are associated with macronutrient intake. Am. J. Clin. Nutr. 82, 1097–101.CrossRefGoogle ScholarPubMed
Lubrano-Berthelier, C., Cavazos, M., Dubern, B.et al. (2003a). Molecular genetics of human obesity-associated MC4R mutations. Ann. N Y Acad. Sci. 994, 49–57.CrossRefGoogle Scholar
Lubrano-Berthelier, C., Durand, E., Dubern, B.et al. (2003b). Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations. Hum. Mol. Genet. 12, 145–53.CrossRefGoogle Scholar
Lubrano-Berthelier, C., Stunff, C., Bougneres, P. & Vaisse, C. (2004). A homozygous null mutation delineates the role of the melanocortin-4 receptor in humans. J. Clin. Endocrinol. Metab. 89, 2028–32.CrossRefGoogle ScholarPubMed
Lubrano-Berthelier, C., Dubern, B., Lacorte, J. M.et al. (2006). Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship and lack of association with binge eating. J. Clin. Endocrinol. Metab. 91, 1811–18.CrossRefGoogle Scholar
Lyons, W. E., Mamounas, L. A., Ricaurte, G. A.et al. (1999). Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc. Natl. Acad. Sci. USA 96, 15 239–44.CrossRefGoogle ScholarPubMed
Mak, H. Y., Nelson, L. S., Basson, M., Johnson, C. D. & Ruvkun, G. (2006). Polygenic control of Caenorhabditis elegans fat storage. Nat. Genet. 38, 363–8.CrossRefGoogle ScholarPubMed
Marks, D. L., Boucher, N., Lanouette, C. M.et al. (2004). Ala67Thr polymorphism in the Agouti-related peptide gene is associated with inherited leanness in humans. Am. J. Med. Genet. A. 126, 267–71.CrossRefGoogle Scholar
Marsh, D. J., Hollopeter, G., Huszar, D.et al. (1999). Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21, 119–22.CrossRefGoogle ScholarPubMed
Martin, N. M., Smith, K. L., Bloom, S. R. & Small, C. J. (2005). Interactions between the melanocortin system and the hypothalamo-pituitary-thyroid axis. Peptides 27, 333–9.CrossRefGoogle Scholar
Mayer, J. (1953). Genetic, traumatic and environmental factors in the etiology of obesity. Physiol. Rev. 33, 472–508.CrossRefGoogle ScholarPubMed
Meyre, D., Bouatia-Naji, N., Tounian, A.et al. (2005). Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat. Genet. 37, 863–7.CrossRefGoogle ScholarPubMed
Michaud, E. J., Bultman, S. J., Klebig, M. L.et al. (1994). A molecular model for the genetic and phenotypic characteristics of the mouse lethal yellow (Ay) mutation. Proc. Natl. Acad. Sci. USA 91, 2562–6.CrossRefGoogle ScholarPubMed
Giudice, Miraglia Del E., Cirillo, G., Nigro, V.et al. (2002). Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity. Int. J. Obes. Relat. Metab. Disord. 26, 647–51.CrossRefGoogle Scholar
Montague, C. T., Farooqi, I. S., Whitehead, J. P.et al. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903–8.CrossRefGoogle ScholarPubMed
Mukhopadhyay, A., Deplancke, B., Walhout, A. J. & Tissenbaum, H. A. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab. 2, 35–42.CrossRefGoogle ScholarPubMed
Naggert, J. K., Fricker, L. D., Varlamov, O.et al. (1995). Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat. Genet. 10, 135–42.CrossRefGoogle ScholarPubMed
Nijenhuis, W. A., Oosterom, J. & Adan, R. A. (2001). AgRP(83–132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol. Endocrinol. 15, 164–71.Google ScholarPubMed
Ollmann, M. M., Wilson, B. D., Yang, Y. K.et al. (1997). Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135–8.CrossRefGoogle ScholarPubMed
Ozata, M., Ozdemir, I. C. & Licinio, J. (1999). Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J. Clin. Endocrinol. Metab. 84, 3686–95.CrossRefGoogle ScholarPubMed
Perusse, L., Rankinen, T., Zuberi, A.et al. (2005). The human obesity gene map: the 2004 update. Obes. Res. 13, 381–490.CrossRefGoogle ScholarPubMed
Poitou, C., Lacorte, J. M., Coupaye, M.et al. (2005a). Relationship between single nucleotide polymorphisms in leptin, IL6 and adiponectin genes and their circulating product in morbidly obese subjects before and after gastric banding surgery. Obes. Surg. 15, 11–23.CrossRefGoogle Scholar
Poitou, C., Viguerie, N., Cancello, R.et al. (2005b). Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition. Diabetologia 48, 519–28.CrossRefGoogle Scholar
Preti, A. (2003). Axokine (Regeneron). IDrugs 6, 696–701.Google Scholar
Pritchard, J. K. (2001). Are rare variants responsible for susceptibility to complex diseases?Am. J. Hum. Genet. 69, 124–37.CrossRefGoogle ScholarPubMed
Saar, K., Geller, F., Ruschendorf, F.et al. (2003). Genome scan for childhood and adolescent obesity in German families. Pediatrics 111, 321–7.CrossRefGoogle ScholarPubMed
Schalin-Jantti, C., Valli-Jaakola, K., Oksanen, L.et al. (2003). Melanocortin-3-receptor gene variants in morbid obesity. Int. J. Obes. Relat. Metab. Disord. 27, 70–4.CrossRefGoogle ScholarPubMed
Seeley, R. J., Drazen, D. L. & Clegg, D. J. (2004). The critical role of the melanocortin system in the control of energy balance. Annu. Rev. Nutr. 24, 133–49.CrossRefGoogle ScholarPubMed
Shiri-Sverdlov, R., Custers, A., Vliet-Ostaptchouk, J. V.et al. (2006). Identification of TUB as a novel candidate gene influencing body weight in humans. Diabetes 55, 385–9.CrossRefGoogle ScholarPubMed
Sleeman, M. W., Anderson, K. D., Lambert, P. D., Yancopoulos, G. D. & Wiegand, S. J. (2000). The ciliary neurotrophic factor and its receptor, CNTFR alpha. Pharm. Acta. Helv. 74, 265–72.CrossRefGoogle ScholarPubMed
Slominski, A., Fischer, T. W., Zmijewski, M. A.et al. (2005). On the role of melatonin in skin physiology and pathology. Endocrine 27, 137–48.CrossRefGoogle ScholarPubMed
Sorensen, T. I. (1995). The genetics of obesity. Metabolism 44, 4–6.CrossRefGoogle ScholarPubMed
Srinivasan, S., Lubrano-Berthelier, C., Govaerts, C.et al. (2004). Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans. J. Clin. Invest. 114, 1158–64.CrossRefGoogle Scholar
Strobel, A., Issad, T., Camoin, L., Ozata, M. & Strosberg, A. D. (1998). A leptin missense mutation associated with hypogonadism and morbid obesity. Nat. Genet. 18, 213–15.CrossRefGoogle ScholarPubMed
Stutz, A. M., Morrison, C. D. & Argyropoulos, G. (2005). The Agouti-related protein and its role in energy homeostasis. Peptides 26, 1771–81.CrossRefGoogle ScholarPubMed
Suviolahti, E., Ridderstrale, M., Almgren, P.et al. (2003). Pro-opiomelanocortin gene is associated with serum leptin levels in lean but not in obese individuals. Int. J. Obes. Relat. Metab. Disord. 27, 1204–11.CrossRefGoogle ScholarPubMed
Swarbrick, M. M., Waldenmaier, B., Pennacchio, L. A.et al. (2005). Lack of support for the association between GAD2 polymorphisms and severe human obesity. PLoS Biol. 3, E315.CrossRefGoogle ScholarPubMed
Tao, Y. X. (2005). Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol. Cell Endocrinol. 239, 1–14.CrossRefGoogle ScholarPubMed
Tartaglia, L. A., Dembski, M., Weng, X.et al. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell 83, 1263–71.CrossRefGoogle ScholarPubMed
Tiwari, H. K. & Allison, D. B. (2003). Do allelic variants of SLC6A14 predispose to obesity?J. Clin. Invest. 112, 1633–6.CrossRefGoogle ScholarPubMed
Vaisse, C., Clement, K., Guy-Grand, B. & Froguel, P. (1998). A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113–14.CrossRefGoogle ScholarPubMed
Vaisse, C., Clement, K., Durand, E., Hercberg, S., Guy-Grand, B. & Froguel, P. (2000). Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J. Clin. Invest. 106, 253–62.CrossRefGoogle ScholarPubMed
Verdich, C., Clement, K. & Sorensen, T. I. (2004). Nutrient-gene interactions in the control of obesity. Funct. Foods Aging Degenerat. Dis. 10, 219–59.Google Scholar
Williamson, D. A., Ravussin, E., Wong, M. L.et al. (2005). Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy. Appetite 45, 75–80.CrossRefGoogle ScholarPubMed
Xu, B., Goulding, E. H., Zang, K.et al. (2003). Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat. Neurosci. 6, 736–42.CrossRefGoogle ScholarPubMed
Yeo, G. S., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G. & O'Rahilly, S. (1998). A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 20, 111–12.CrossRefGoogle ScholarPubMed
Yeo, G. S., Lank, E. J., Farooqi, I. S., Keogh, J., Challis, B. G. & O'Rahilly, S. (2003). Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms. Hum. Mol. Genet. 12, 561–74.CrossRefGoogle ScholarPubMed
Yeo, G. S., Connie Hung, C. C., Rochford, J.et al. (2004). A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci. 7, 1187–9.CrossRefGoogle Scholar
Yiannakouris, N., Melistas, L., Kontogianni, M., Heist, K. & Mantzoros, C. S. (2004). The Val81 missense mutation of the melanocortin 3 receptor gene, but not the 1908C/T nucleotide polymorphism in lamin A/C gene, is associated with hyperleptinaemia and hyperinsulinaemia in obese Greek caucasians. J. Endocrinol. Invest. 27, 714–20.CrossRefGoogle ScholarPubMed
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L. & Friedman, J. M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–32.CrossRefGoogle ScholarPubMed

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